Involvement of the NO-cGMP-K Channels Pathway in Cardioprotective Effects of Baccharis milleflora in Hypertensive Rats

Cardiovascular diseases are the leading causes of deaths worldwide. Complementary therapies, such as medicinal plants, have become increasingly common among treatment options. We propose to investigate the cardioprotective effects of the ethanol-soluble fraction obtained from the aerial parts of <i>Baccharis milleflora</i> in hypertensive rats. Cladodes of <i>B. milleflora</i> were collected, and the aqueous extract was obtained by infusion. The infusion was then treated with ethanol, resulting in the ethanol-soluble fraction of <i>B. milleflora</i>, which was analyzed by LC-DAD-MS. The MS and MS/MS data obtained from the ethanol-soluble fraction of <i>B. milleflora</i> was submitted to the Global Natural Products Social Molecular Networking platform to generate the molecular network, and three main clusters were detected. Wistar-Kyoto and spontaneously hypertensive rats were divided into different experimental groups, including naïve, control (vehicle), hydrochlorothiazide (25 mg/kg), and ethanol-soluble fraction of <i>B. milleflora</i> (30, 100, and 300 mg/kg). The treatment lasted for 28 days. At the end of the treatment, the animals underwent evaluation of renal function, electrocardiographic profile, blood pressure, mesenteric vascular reactivity, serum biochemical parameters, and histopathological analysis. The molecular pathways involved in pharmacological activity were also investigated. After 28 days, animals treated with ethanol-soluble fraction of <i>B. milleflora</i> 30 mg/kg showed a significant antioxidant, diuretic, and antihypertensive response, as well as reversed endothelial dysfunction and left ventricular hypertrophy induced by hypertension. Treatment with a non-selective NO synthase inhibitor, cGMP inhibitor, or non-selective K+ channel blocker suppressed the antihypertensive effects of ethanol-soluble fraction of <i>B. milleflora</i>. Our findings showed that <i>B. milleflora</i> is a species with cardioprotective activity when administered for a prolonged period to hypertensive rats.